| Summary: | 碩士 === 中國醫藥大學 === 醫學檢驗生物技術學系碩士班 === 102 === The prevalence of hepatitis C virus (HCV) infection is all around the
word. Until now, over 170 million people were infected by HCV. The virus
causes liver diseases such as chronic hepatitis, cirrhosis, and liver cancer. The
standard therapy of HCV is pegylated-interferon (Peg-IFN) combined with
ribavirin (RBV), but only 50% sustained viral response for HCV genotype
1(GT1). Boceprevir and Telaprevir, which are two linear ketoamide
compounds, which covalently bind to the serine protease active-site of HCV
NS3, have been approved by FDA to treat HCV infection in 2011. In clinical,
these two inhibitors induce HCV genotype 1 virus NS3 protease mutation.
The aim of the study is to establish a HCV GT1 NS3/4A protease antiviral
screening assay. The wild-type HCV genotype 1 NS3 protease and common
resistance sites in clinical of the NS3 protease had been constructed and the
expressions were determined by Western blotting. The activities of wild type
and mutant NS3 protease were determined by Western blotting and high
throughput cell–based luciferase assay. The high throughput drug selection
system will be applied to the NS3 proteinase inhibitors that exclude viral
escape through common resistance sites in clinic.
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